Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 14) Duration of Therapy and Treatment Failure Until recently, there was little incentive to establish the most appropriate duration of treatment; patients were instructed to take a 7- or 10-day course of treatment for most common infections. A number of recent investigations have evaluated shorter durations of therapy, especially in patients with community- acquired pneumonia. Table 127-10 lists common bacterial infections for which treatment duration guidelines have been established or for which there is sufficient clinical experience to establish treatment durations. The ultimate test of cure for a bacterial infection is the absence of relapse when therapy is discontinued. Relapse is defined as a recurrence of infection with the identical organism that caused the first infection. In general, therefore, the duration of therapy should be long enough to prevent relapse yet not excessive. Extension of therapy beyond the limit of effectiveness may increase the medication's side effects and encourage the selection of resistant bacteria. The art of treating bacterial infections lies in the ability to determine the appropriate duration of therapy for infections that are not covered by established guidelines. Re-treatment of infections for which therapy has failed usually requires a prolonged course (>4 weeks) with combinations of antibacterial agents. Table 127-10 Duration of Therapy for Bacterial Infections Duration of Therapy Infections Single dose Gonococcal urethritis, streptococcal pharyngitis (penicillin G benzathine), primary and secondary syphilis (penicillin G benzathine) 3 days Cystitis in young women, community- or travel- acquired diarrhea 3–10 days Community-acquired pneumonia (3–5 days), community- acquired meningitis (pneumococcal or meningococcal), antibiotic- associated diarrhea (10 days), Giardia enteritis, cellulitis, epididymitis 2 weeks Helicobacter pylori– associated peptic ulcer, neurosyphilis (penicillin IV), penicillin-susc eptible viridans streptococcal endocarditis (penicillin plus aminoglycoside), disseminated gonococcal infection with arthritis, acute pyelonephritis, uncomplicated S. aureus catheter- associated bacteremia 3 weeks Lyme disease, septic arthritis (nongonococcal) 4 weeks Acute and chronic prostatitis, infective endocarditis (penicillin-resistant streptococcal) >4 weeks Acute and chronic osteomyelitis, S. aureus endocarditis, foreign-body infections (prosthetic- valve and joint infections), relapsing pseudomembranous colitis Mechanisms to Optimize Antimicrobial Use Antibiotic use is often not "rational," and it is easy to understand why. The diagnosis of bacterial infection is often uncertain, and patients may expect or demand antimicrobial agents in this tenuous situation. There is a bewildering array of drugs, each with claims of superiority over the competition. The rates of resistance for many bacterial pathogens are ever-changing, and even experts may not agree on the clinical significance of resistance in some pathogens. Investigations consistently report that ~50% of antibiotic use is in some way "inappropriate." Aside from the monetary cost of using unnecessary or overly expensive antibiotics, there are the more serious costs associated with excess morbidity from superinfections such as C. difficile disease, adverse drug reactions, drug interactions, and selection of resistant organisms. Although these costs are not yet well quantified, they add substantially to the overall costs of medical care. At a time when fewer new antimicrobial drugs are entering the worldwide market than in the past, much has been written about the continued rise in rates of resistant microorganisms and its causes. The message seems clear: the use of existing and new antimicrobial agents must be more judicious and infection control more effective if we are to slow or reverse trends in resistance. The phrase antimicrobial stewardship is used to describe the new attitude toward antibacterial agents that must be adopted to preserve their usefulness. Appropriate stewardship requires that these drugs be used only when necessary, at the most appropriate dosage, and for the most appropriate duration. Increasing attention is being given to the relationships between differences in antibiotic consumption and differences in rates of resistance in different countries. While some newer antibacterial drugs undeniably represent important advances in therapy, many offer no advantage over older, less expensive agents. With rare exceptions, newer drugs are usually found to be no more effective than the comparison antibiotic in controlled trials, despite the "high prevalence of resistance" often touted to market the advantage of the new antibiotic over older therapies. The following suggestions are intended to provide guidance through the antibiotic maze. First, objective evaluation of the merits of newer and older drugs is available. Online references such as the Johns Hopkins website (http://hopkins- abxguide.org) offer current and practical information regarding antimicrobial drugs and treatment regimens. Evidence-based practice guidelines for most infections are available from the Infectious Diseases Society of America (www.idsociety.org). Second, clinicians should become comfortable using a few drugs recommended by independent experts and professional organizations and should resist the temptation to use a new drug unless the merits are clear. A new antibacterial agent with a "broader spectrum and greater potency" or a "higher serum concentration-to-MIC ratio" will not necessarily be more clinically efficacious. Third, clinicians should become familiar with local bacterial susceptibility profiles. It may not be necessary to use a new drug with "improved activity against P. aeruginosa" if that pathogen is rarely encountered or if it retains full susceptibility to older drugs. Fourth, a skeptical attitude toward manufacturers' claims is still appropriate. For example, rising rates of penicillin resistance in S. pneumoniae have been used to promote the use of broader-spectrum drugs, notably the fluoroquinolones. However, except in patients with meningitis, amoxicillin is still effective for infections caused by these "penicillin-resistant" strains. Finally, with regard to inpatient treatment with antibacterial drugs, a number of efforts to improve use are under study. The strategy of antibiotic "cycling" or rotation has not proved effective, but other strategies, such as heterogeneity or diversity of antibiotic use, may hold promise. Adoption of other evidence-based strategies to improve antimicrobial use may be the best way to retain the utility of existing compounds. For example, appropriate empirical treatment of the seriously ill patient with one or more broad-spectrum agents is important for improving survival rates, but therapy may often be simplified by switching to a narrower-spectrum agent or even an oral drug once the results of cultures and susceptibility tests become available. While there is an understandable temptation not to alter effective therapy, switching to a more specific agent once the patient's clinical condition has improved does not compromise outcome. A promising and active area of research includes the use of shorter courses of antimicrobial therapy. Many antibiotics that once were given for 7–10 days can be given for 3–5 days with no loss of efficacy and no increase in relapse rates (Table 127-10). Adoption of new guidelines for shorter-course therapy will not undermine the care of patients, many unnecessary complications and expenses will be avoided, and the useful life of these valuable drugs will perhaps be extended. Further Readings Bartlett JG, Perl TM: The new Clostridium difficile— What does it mean? N Engl J Med 353:2503, 2005 [PMID: 16322604] Cosgrove SE, Carmeli Y: The impact of antimicrobial resistance on health and economic outcomes. Clin Infect Dis 36:1433, 2003 [PMID: 12766839] Fishman N: Antimicrobial stewardship. Am J Med 119:S53, 2006 Gruchalla RS, Pirmohamed M:Antibiotic allergy. N Engl J Med 354:601, 2006 [PMID: 16467547] Jacoby GA, Munoz-Price LS: The new β- lactamases. N Engl J Med 352:380, 2005 [PMID: 15673804] Kollef M:Appropriate empirical antibacterial therapy for nosocomial infections: Getting it right the first time. Drugs 63:2157, 2003 [PMID: 14498753] Nahum GG et al: Antibiotic use in pregnancy and lactation: What is and i s not known about teratogenic and toxic risks. Obstet Gynecol 107:1120, 2006 [PMID: 16648419] Peterson LR: Penicillins for treatment of pneumococcal pneumonia: Does in vitro resistance really matter? Clin Infect Dis 42:224, 2006 [PMID: 16355333] Polk H C Jr:Continuing refinements in surgical antibiotic prophylaxis. Arch Surg 140:1066, 2005 [PMID: 16301441] Ray WA et al: Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 351:1089, 2004 [PMID: 15356306] Bibliography File TM Jr: Clinical efficacy of newer agents in short- duration therapy for community-acquired pneumonia. Clin Infect Dis 39(Suppl 3):S159, 2004 Linder JAet al: Fluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med 118:259, 2005 [PMID: 15745724] Rybak MJ: Pharmacodynamics: Relation to antimicrobial resistance. Am J Med 119(6 Suppl 1):S37, 2006 . Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 14) Duration of Therapy and Treatment Failure Until recently, there was. Re -treatment of infections for which therapy has failed usually requires a prolonged course (>4 weeks) with combinations of antibacterial agents. Table 127- 10 Duration of Therapy for Bacterial. duration of treatment; patients were instructed to take a 7- or 10-day course of treatment for most common infections. A number of recent investigations have evaluated shorter durations of therapy,